refractoriness. Am J Cardiol 1988;62:1192-1198. 6. Kerr CR, Strauss, HC. The measurement of sinus node refractoriness in man. Circulation 1983;88:1231-1237. 7. Kerr CR, Strauss HC, Aiama N. Effect of basic pacing cycle length on sinus node refractoriness in the rabbit. Am J Cardiol 1985;56:162-7. 6. Kerr CR, Prsytowsky EN, Brauwing DJ, Strauss HC. Characteristics of refractoriness in the sinus node of the rabbits. Circ Res 1980;470:742-756. 9. Cramer M, Siegel M, Bigger JT Jr, Hoffman BF. Characteristics of extracellu- lar potentials recorded from the sinoatrial pacemaker of the rabbit. Circ Res

1977;41:292-299. 10. Cramer M, Hariman RJ, Boxer R, Hoffman BF. Electrogram from the canine sinoatrial pacemaker recorded in-vitro and in-situ. Am J Cardiol 1978;43:939-946. Il. Reiffel JA, Bigger JT Jr. Current status of direct recordings of the sinus node electrogram in man. PACE 1983;6:1143-1150. 12. Reiffel JA, Zimmerman G. The duration of the sinus node depolarization on transvenons sinus node elcctrograms can identify sinus node dysfunction and can suggest its severity. PACE 1989;12:174661756.

Survival In Patients Declining Implantable Cardioverter-Defibrillators Sergio L. Pinski, MD, Elena B. Sgarbossa, MD, James D. Maloney, fv!b, and Richard G. Trohman, MD

P revious studies have suggested that the implanta- ble cardioverter-defibrillator (ICD) significantly prolongs survival in patients with malignant ven-

tricular arrhythmias. 1-3 Design limitations inherent in studies without internal controls make results difficult to interpret.4 Randomized trials would be ideal to define the benefits derived from ICDs, but there has been reluc- tance to initiate such trials. In this study, we used patients who declined ICD implant as a control population to assess results of ICD therapy.

All 77 patients with malignant arrhythmias for whom we recommended ICDs during 1989 were re- viewed. Sixty-seven had drug-refractory arrhythmias and IO had cardiac arrest without inducible sustained ventricular tachycardia. Arrhythmia-related deaths were defined as the sum of sudden deaths, operative deaths (within 30 days of the procedure or before hospital discharge), arrhythmic nonsudden deaths (within 24 hours after having ventricular arrhythmias terminated by dejibrillation),j and deaths due to anti- arrhythmic drug toxicity. Values are presented as mean f standard deviation. Comparisons were per- formed by means of Student’s, chi-square or Fisher’s tests. Analysis of survival was performed by the Kaplan-Meier and Mantel-Haenszel methods. A p value <0.05 was considered significant.

18 f 7 months. In group A, 3 patients eventually received an ICD and were withdrawn from follow-up at that time. Two had ventricular tachycardia recur- rences requiring cardioversion. Another opted for an ICD after 3 months. There were 3 deaths in group A. A patient treated with amiodarone had cardiac arrest at home. She was defibrillated and taken to a hospi- tal. An electrocardiogram suggested acute myocardi- al infarction. She died in electromechanical dissocia- tion after several recurrences of ventricular jibrilla- tion. One patient died of heart failure and another from gastrointestinal bleeding. There were 10 deaths in group B (6 were arrhythmia-related). Five patients died postoperatively (4 after initial implant and 1 after removal of infected patches) and I died in the hospital after several episodes of ventricular tachy- cardia. The other 4 died of heart failure. Survival at 12 and 18 months was 78 f 12, and 78 f 15, respec- tively, in group A and 85 f 4 and 84 f 5, respectively, in group B (p = not significant). Freedom from ar- rhythmia-related death was 91 f 9 and 91 f 10 in group A and 90 f 4 and 90 f 4 in group B (p = not significant).

Our series suggests that, in the short term, the use of ICDs does not lead to a dramatic decrease in total or

Fifteen patients (19%) declined ICD implant (group A). The remaining 62 patients (81%) under-

TABLE I Comparison Between Group A and B Patients

went the procedure (group B). Groups did not differ Group A- Group B- Declined ICD ICD

Hemodynamically unstable sustained ventricular tachycardia (cycle length 322 f 53 ms) was inducible

significantly when variables were compared (Table I).

on the discharge regimen in 12 patients. In 3, the

Eight patients in group A were discharged taking amiodarone; 6 were discharged taking amiodarone and a class I drug, and 1 patient was given quinidine.

Cardiac arrest (%) 4 (27) 23 (37) Hemodynamically significant VT (%) 6 (40) 31 (50) NS Syncope with inducible sustained

(n = 15)

5 (33)

(n = 62)

8 (13)

Age (years)

I monomorphic VT (%I

64 f 4 62 f 8 NS Men/women 14/l 50/12 NS Coronary artery disease (%) 13 (87) 47 (76) NS Clinical oresentation

- 1

regimen was not tested. Patients were followed up for Left ventricular’ejection fraction (%) 31 2 15 34 + 15 NS Cycle length of induced sustained 289 f 70* 284r 65t NS

I -̂ _ -̂̂ “_L:̂ \I_ ‘ns)

From the Department of Cardiology, Desk F-15, The Cleveland Clinic Illull”rll”rpI111; “I ,I

Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195. Manuscript Failed antiarrhythmic drug trials 2.9 z 1.3 2.4 2 1.3 NS

received March 21, 1991; revised manuscript received and accepted *n = 13; Ttl = 43. ICD = implantable cardioverter-defibrillator; NS = not significant; VT = ventricular tachycardia.

May 24, 1991.

800 THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 68 SEPTEMBER 15, 1991

arrhythmia-related mortality. However, it lacks statisti- cal power to detect small but significant differences be- tween treatments. Indications for ICDs agreed with those generally accepted. Although our design does not protect from bias as well as randomization does, groups were similar in several prognostically important vari- ables, supporting the validity of the comparison. Our 6% operative mortality seems high, but we applied more stringent criteria for its definition than others have u~ed.~~~ Amiodarone was given to all but 1 of the patients who declined an ICD. Electrophysiologic studies are use- ful in assessing the effects of amiodarone therapy, but have a suboptimal specificity for predicting treatment failures.6

The effects of ICD therapy on patient survival have been explored by comparing patients treated with ICDs with control subjects treated before ICD availability.3 The main limitation of this approach is that comparabil- ity between groups cannot be ensured. Referral patterns, supportive care and alternative therapies change over time. Other studies have used patients with ICDs as their own control subjects by comparing actual to estimated survival based on the time of the first shock received.‘13 This design overestimates the efficacy of ICDs. Current- ly approved devices do not store the electrograms that trigger discharges. Thus, the appropriateness of sponta- neous shocks is a matter of clinical judgment. Even shocks confirmed appropriate by electrocardiography cannot always be equated with death. Many recurrences of ventricular tachycardia in patients taking antiarrhyth- mic drugs are relatively well-tolerated. Furthermore, pa- tients with ICDs do not always receive concomitant best alternative therapy.

Most of these shortcomings can be avoided by the use of patients who declined ICD implant as control subjects. As stated by Feinstein, 7 “a patient who fails to carry out the doctor’s recommendations is performing an impor- tant experiment that the doctor was unwilling to under- take.” Behringer et al* recently reported a poor outcome

in 18 patients declining ICDs. Several differences be- tween their study and ours may explain the opposite conclusions. Their patients were treated between 1983 and 1989, whereas all our patients were seen during 1989. They treated 5 patients (28%) with only class I drugs, 4 of whom died suddenly. Only 1 of our patients (7%) was treated with quinidine. Finally, since they did not provide characteristics of their patients receiving ICDs during the same period, population bias cannot be ruled out.

The value of ICDs in the management of patients with malignant arrhythmias is still being elucidated. The favorable early experience with these devices warrants the performance of extensive randomized trials compar- ing ICDs with other therapies. We are aware of 2 trials being conducted abroad and of attempts to launch a multicenter trial in the United States. Hopefully, these trials will shed further light on the role of ICDs in pa- tients with malignant ventricular arrhythmias.

1. Tchou PJ, Kadri N, Anderson J, Caceres JA, Jayazeri M, Akhtar M. Auto- matic implantable cardioverter-defibrillators and survival of patients with left ventricular dysfunction and malignant ventricular arrhythmias. Ann Intern h4ed 1988;109:529-534. 2. Winkle RA, Mead H, Ruder MA, Guadiani VA, Smith NA, Buch WS, Schmidt P, Shipman T. Long-term outcome with the automatic implantable cardioverter-defibrillator. J Am Coil Cardiol 1989;13:1353-1361. 3. Fogoros RN, Elson JJ, Bonnet CA, Fiedler SB, Burkholder JA. Efficacy of the automatic implantable cardioverter-defibrillator in prolonging survival in patients with severe underlying cardiac disease. J Am Coil Cardio/ 1990;16:381-386. 4. Bailar JC III, Louis TA, Lavori PW, Polansky M. Studies without internal controls. N Engl J Med 1984;311:156-162. 5. Kim SG, Fisher JD, Furman S, Gross J, Zilo P, Roth JA, Ferrick KJ, B&man R. Benefits of implantable detibrillators are overestimated by sudden death rates and better represented by the total arrhythmic death rate. J Am Co11 Cardiol 1991;17:1587-1592. 6. Kreamer JW, Zevitz M, Somberg JC. The role of electrophysiologic testing in the selection of amiodarone therapy. J Ckn Phnrmacol 1989;29:429-435. 7. Feinstein AR. “Compliance bias” and the interpretation of therapeutic trials. In: Haynes RB, Taylor DW, Sack&t DL, eds. Compliance in Health Care. Baltimore, MD: The Johns Hopkins University Press, 1979:309-322. 6. Behringer D, Aarons D, Veltri E. Outcome of patients with refractory ventricu- lar tachyarrhythmias declining automatic implantable cardioverter-defibrillator (abstr). J Am Co11 Cardiol 1991;17:351A.

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